Overview
Glecaprevir is a hepatitis C virus nonstructural protein protease inhibitor suggested by AbbVie and Enanta Pharmaceuticals. It is used in chronic hepatitis C virus cases. It is used along with Pibrentasvir, as it can work as a potent antiviral agent against significant hepatitis C virus genotypes.
Together they are marketed as Mavyret. AbbVie suggested the Glecapravir-Pibrentasir combination as Mavyret in December 2016 to treat hepatitis C virus genotypes. Further, it was approved by the Food and Drug Administration (FDA) in august 2017. Europe also supports it in august 2017 under the trade name of Maviret.
What Is the Hepatitis C Virus?
Hepatitis is an inflammation of the liver in which swelling of the liver tissues occurs upon getting injured or infected. There are different types of hepatitis infections. The Hepatitis C virus causes hepatitis C infection. The disease can be mild for a week to severe for lifelong illness. The hepatitis C virus can cause acute and chronic hepatitis.
Acute can be short-term, with six months lasting. It occurs when the infection goes away after a few months. Chronic can be long-term with long-lasting effects. It occurs when the infection is not treated and worsens with more health problems, like liver damage, cirrhosis, and death.
What Are the Symptoms of the Hepatitis C Virus?
Symptoms of hepatitis C virus infection are:
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Dark yellow urine.
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Fatigue.
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Fever.
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Gray or clay color stools.
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Loss of appetite.
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Nausea and vomiting.
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Pain in the abdomen.
How Is the Hepatitis C Virus Acquired?
It is acquired by:
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Sharing the same needle as the infected hepatitis person.
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The accidental needle pricked the hepatitis-infected person.
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Having the tattoo with the same needle as the infected person's needle.
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A mother with hepatitis delivers an infected baby.
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Having unprotected sex with the hepatitis-infected person.
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Getting a blood transfusion from an infected hepatitis person.
How Is Hepatitis C Virus Infection Diagnosed?
The doctor can diagnose the hepatitis C virus by taking a medical history, laboratory blood tests, and additional tests for the liver. The liver test can be a liver ultrasound or liver biopsy.
How Does Glecaprevir Work in Hepatitis Cases?
Glecaprevir is a hepatitis C virus protein NS3/4A protease inhibitor drug. It works by decreasing the amount of hepatitis C virus (HCV) in the body by targeting viral RNA replication. And Pibrentasvir is a hepatitis C virus NS5A inhibitor. It stops the hepatitis C virus spread.
What Is the Use of Glecaprevir Medicine?
Uses
Glecaprevir is used to treat chronic hepatitis C virus with genotypes 1,2,3,4,5 or 6 infections without cirrhosis or cirrhosis.
Dosage:
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Dose of Administration - oral.
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Dose Strength - 100 mg with Pibrentasvir 40 mg.
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Dose Form - tablets and packets
The Recommended Dosage for Adults
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Three tablets are taken daily with food (Glecaprevir 300 mg and Pibrentasvir 120 mg).
Recommended Dosage in Pediatric:
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Children from 3 years to 12 years should be given oral pellets according to body weight. There are specific dosing guidelines based on body weight for the pediatric population.
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Children above 12 years of age are recommended the same dose as adults.
Contraindications of Glecaprevir:
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It is contraindicated if the patient is allergic to Glecaprevir.
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Patient with severe hepatic impairment.
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Prohibited to take along with Rifampicin or Atazanavir.
Warning and Precautions:
Patients with Liver Diseases
Patients who suffer hepatic decompression or failure should discontinue the Glecaprevir drug.
Alcohol
The overuse of alcohol or addiction to it can be problematic with the Glecaprevir drug.
Diabetes
Patients with diabetes are also recommended to use Glecaprevir cautiously.
Risks of Hepatitis Reactivation
The patient must be appropriately diagnosed with hepatitis B or C virus infection.
Special Considerations:
Allergies
Food, dyes, preservatives, medicine, or animal allergies come under the category. If the patient has any of it, the patient should notify the doctor before the drug use.
Pediatric Patients
Children under three are not allowed to have the Glecaprevir and Pibrentsavir combination. The safest and efficacy are not clarified for children under three years of age.
Geriatric Patients
The use of medicine in older patients can not be as helpful because of other medical conditions.
Breastfeeding Mother
No studies on breastfeeding mothers related to this medicine have been done, hence not determining the effects on infants.
Drug Interactions
Certain medicines like Rifampicin or Atazanavir are not taken. The doctor should know about the medication the patient is taking before he suggests this medicine.
For Patients -
What Is Glecapravir?
Glecaprevir is a hepatitis C virus NS3/4A protease inhibitor medicine. It is a direct-acting antiviral agent that targets viral RNA replication. It is used along with the Pibrentasvir, a hepatitis C virus NS5A inhibitor. The combination of both medicines is named Mavyret. It treats chronic hepatitis C virus infections with or without cirrhosis.
Why Is it Prescribed?
Glecaprevir with Pibrentasvir is used to treat severe or chronic hepatitis C infections in adults and children. It is used in children older than three years of age. As Glecaprevir is a protease inhibitor, it works by decreasing the amount of the hepatitis C virus. In the body. And the use of Pibrentasvir works coordinatedly with it to stop the spread of the hepatitis C virus in the body.
How Is Medicine Used?
Glecaprevir with Pibrentasvir is done in the form of tablets or pellets and taken by mouth. It should be taken with food once daily. It is recommended for 8 to 16 weeks. After that, the doctor prescribes the tablet's dosages according to the case. After that, take the dose as defined by the doctor. Do not take it more or less by yourself.
How Is Medicine Taken?
A dose of Glecaprevir and Pibrentasvir pellets is taken with soft foods by sprinkling the pellet packet on the food, such as cheese, jam, spread, and peanut butter. Do not mix the pellet in liquid stuff that may dissolve fast. Leave the mix for 15 minutes. Do not mix the medicine to dissolve it, as it will give a bitter taste to eating food. If the medicine is stuck in the bowl, add more food to engulf it. Do not chew the food, as it will cause bitterness in chewing.
What Are the Precautions While Having Glecaprevir?
Precautions while having it are,
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Taking the dose as recommended by your doctor.
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Taking medicine with soft foods without chewing.
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Taking medicine at the same time every day is routine.
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Do not stop taking the medication yourself; consult the doctor before withdrawing it.
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Do go for the regular follow-up visit to the doctor.
What Should Your Doctor Know Before He Recommends Glecapravir?
Inform your doctor before recommending Glecaprevir are,
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If you are allergic to Glecaprevir.
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Inform your doctor if you are taking Atazanavir or Rifampicin.
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Do inform your doctor if you are taking blood thinners medicine.
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Inform the doctor about the liver infection or disease if you are suffering.
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If you have them, inform the doctor about diabetes or human immunodeficiency virus (HIV).
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Inform your doctor about the pregnancy, if you are planning it, or if you are breastfeeding your baby.
What Diet Should You Follow While Taking Glecaprevir?
You should continue your regular diet as you are taking it. But if your doctor suggests you have a supplementary diet, you can go for it.
What if You Miss Your Regular Dose?
If you miss your dose on a routine, then take it as soon as possible to remember. However, if the timings of the next dose are near, you should skip the missed dose and have the next one at a regular time. Avoid taking a double dose at nearby times.
How to Store Medicine?
The medicine should be stored in a tightly closed container. The medicine should be kept away from the children's approach and sight. It is essential that the children not engulf the medicine as it can lead to child poisoning. The storage should be at room temperature, where no excess heat and moisture come.
How to Dispose of Medicine?
Mentioned particular safeThe unwanted medicine should be disposed of safely so that no pets, children, or any other consume it unknowingly. The Food and Drug Administration has provided safe disposal of medical information. Or you can learn the take-back program for medicine disposal. But do not flush out the medicine in the toilets.
Side effects are,
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Headache.
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Weakness.
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Tiredness.
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Nausea and vomiting.
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Diarrhea.
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Allergic reactions.
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Swelling over the face, tongue, or throat.
What Are the Unusual Side Effects That Require Doctor Attention?
Unusual side effects that require doctor attention are,
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Confusion.
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Sleepiness.
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Swelling of the stomach area.
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Blood vomitings.
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Dark, black, or bloody stools.
What Are the Effects of an Overdose of Medicine?
If you take an overdose and some effects are seen, consult your doctor as soon as possible.
Some effects are:
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Seizures.
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Collapse.
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Faint.
What Are the Important Points to Know About Medicine?
Important points about the medicine are,
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Inform the doctor about all the medication you are taking, including your supplements of vitamins and minerals.
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Do inform the doctor about your medical conditions; tell your doctor if you have diabetes or hypertension.
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Take medicine as recommended by the doctor, do not take it more or less by yourself.
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Inform your doctor about the side effects you are suffering after medicine intake.
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Take medicine with soft foods only.
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Do not stop taking medication by yourself; consult the doctor before it.
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Do not share the treatment with others.
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Do not throw the medicine anywhere. Go for a take-back program.
Can Glecapravir Alone Cure Hepatitis C Virus Infection?
No, Glecapravir alone can not cure the hepatitis infection. Glecaprevir and Pibrentasvir are used to treat the hepatitis C virus. Mavyret is the marketed name of the medicine, having both Glecaprevir and Pibrentasvir medicine.
Is Glecapravir Safe to Have?
Yes, Glecaprevir is a safer and more effective medicine for hepatitis C virus cure. However, side effects do appear while taking medication, but it cures the hepatitis infection.
For Doctors -
What Are the Properties of Glecaprevir?
The chemical properties of the Glecaprevir are:
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It is a small molecule.
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It is nonstructural.
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Its average weight is 838.87.
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It has monoisotopic 838. 298310911.
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The chemical formula is C38H46F4N6O9S.
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The half-life of the Glecaprevir drug is six hours.
What Is the Indication of the Glecaprevir Drug?
Indication of Glecaprevir is:
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It is used in treating adult patients with chronic hepatitis C virus genotypes 1,2,3,4,5, and 6 with or without cirrhosis.
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It is also indicated in treating patients with HCV genotype one infection who were previously treated with inhibitors containing hepatitis C virus NS5A or NS3/4A protease inhibitors.
What Is the Pharmacodynamics of the Glecaprevir Drug?
Mechanism of Action of the Glecaprevir Drug
Glecaprevir is an inhibitor of the hepatitis C virus, NS3/4A protease. This protease is a viral enzyme needed for proteolytic cleavage of the hepatitis C virus to mature forms of NS3, NS4A, NS4B, NS5A, and NS5B proteins. These proteins are essential for the replication of the virus.
There are two terminals of the NS3 proteins; the N-terminal confers the serine protease activity, while the C-terminal confers a DExH/D-box RNA helicase which takes NTP energy to form RNA during the replication of viral genomic RNA. NS4A is a cofactor for NS3 that directs the localization of NS3 along with enzymatic acts. Glecapravir disturbs the virus's intracellular processes by prohibiting the NS3/4A protease activity of cleaving polypeptides and the proteolytic process of mature proteins.
Absorption
Glecapravir takes nearly 5 hours to reach the peak plasma concentration. The mean peak plasma concentration is 597 ng/mL in the non-cirrhotic hepatitis C virus population. Therefore, the consumption of meals increases the absorption of Glecaprevir by 83-163 %.
Distribution
No information is present regarding the distribution of the drug.
Metabolism
Glecaprevir limits secondary metabolism, especially by CYP3A.
Elimination
Although the route of elimination is mostly biliary-fecal, approximately 92 percent of the drug dose is excreted in feces. Still, nearly 0.7 percent of the drug is excreted in urine also.
Dosage
Glecaprevir is taken orally by adults and children. There are two forms of oral intake, tablet form, and pellet form.
Oral Dosage for Tablet Form
For Hepatitis C Virus Infection
Adults and children above 12 years of age or who weigh 45 kilograms or more are recommended three tablets (total dose of 300 milligrams of Glecaprevir and 120 milligrams of Pibrentasvir) once a day for eight weeks. Each tablet has 100 milligrams of Glecaprevir and 40 milligrams of Pibrentasvir).
For Hepatitis C Virus Infection, Patients Who Have Previously Been Treated With Other Drugs
Adults and children who are above 12 years of age or have a weight of 45 kilograms or more are recommended three tablets total dose of 300 milligrams of Glecaprevir and 120 milligrams of Pibrentasvir) once a day for 8 to 16 weeks. Each tablet has 100 milligrams of Glecaprevir and 40 milligrams of Pibrentasvir).
Patients With Kidney Or Liver Problems
Adults and children who are above 12 years of age or have a weight of 45 kilograms or more are recommended three tablets total dose of 300 milligrams of Glecaprevir and 120 milligrams of Pibrentasvir) once a day for 12 to 16 weeks. Each tablet has 100 milligrams of Glecaprevir and 40 milligrams of Pibrentasvir).
Oral Dosage for Pellet Form
For Hepatitis C Virus Infection
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The doctor should determine the child's dose if the child is younger than three years of age. If children from 3 to 12 years of age weigh less than 45 kg, then the dose is determined by the doctor on their weight.
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Suppose the child has 30 to 45 kilograms of weight - 5 packets (total dose of 250 milligrams of Glecaprevir and 100miligram of Pibrentasvir) once a day for eight weeks. Each packet contains 50mg of Glecaprevir and 20 mg of Pibrentasvir.
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Suppose the child weighs 20 to 30 kilograms of weight - 4 packets (total dose of 200mg of Glecaprevir and 80 mg of Pibrentasvir) once a day for eight weeks. Each packet contains 50 mg of Glecaprevir and 20 mg of Pibrentasvir.
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Suppose the child weighs less than 20 kilograms - 3 packets (total dose of 200mg of Glecaprevir and 60 mg of Pibrentasvir) once a day for eight weeks. Each packet contains 50 mg of Glecaprevir and 20 mg of Pibrentasvir.
For Hepatitis C Virus Infections That Have Been Previously Treated With Other Drugs
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If the child is younger than three years of age, the doctor should determine the child's dose. If children from 3 to 12 years of age weigh less than 45 kg, then the dose is determined by the doctor on their weight.
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Suppose the child has 30 to 45 kilograms of weight - 5 packets (total dose of 250 milligrams of Glecaprevir and 100miligram of Pibrentasvir) once a day for 8 to 16 weeks without cirrhosis and 12 to 16 weeks for patients with cirrhosis. Each packet contains 50mg of Glecaprevir and 20 mg of Pibrentasvir.
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If the child weight 20 to 30 kilograms of weight - 4 packets (total dose of 200mg of Glecaprevir and 80 mg of Pibrentasvir) once a day for 8 to 16 weeks without cirrhosis and 12 to 16 weeks for patients with cirrhosis. Each packet contains 50 mg of Glecaprevir and 20 mg of Pibrentasvir.
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If the child weighs less than 20 kilograms - 3 packets (total dose of 200mg of Glecaprevir and 60 mg of Pibrentasvir) once a day for 8 to 16 weeks without cirrhosis and 12 to 16 weeks for patients with cirrhosis. Each packet contains 50 mg of Glecaprevir and 20 mg of Pibrentasvir.
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For Patients With Kidney or Liver Issues - The doctor should determine the child's dose if the child is younger than three years of age. If children from 3 to 12 years of age weigh less than 45 kg, then the dose is determined by the doctor on their weight.
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Suppose the child has 30 to 45 kilograms of weight - 5 packets (total dose of 250 milligrams of Glecaprevir and 100miligram of Pibrentasvir) once a day for eight weeks. Each packet contains 50mg of Glecaprevir and 20 mg of Pibrentasvir.
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Suppose the child weighs 20 to 30 kilograms - 4 packets (total dose of 200mg of Glecaprevir and 80 mg of Pibrentasvir) once a day for eight weeks. Each packet contains 50 mg of Glecaprevir and 20 mg of Pibrentasvir.
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Suppose the child weighs less than 20 kilograms - 3 packets (total dose of 200mg of Glecaprevir and 60 mg of Pibrentasvir) once a day for eight weeks. Each packet contains 50 mg of Glecaprevir and 20 mg of Pibrentasvir.
Special Considerations:
Allergies
Allergies can be from any food, dyes, preservatives, medicine, or animal. If the patient has any of it, the patient should notify the doctor before the drug use as cautious use of Glecaprevir drug is done on them.
Pediatric Patients
Children under three are not allowed to have the Glecaprevir and Pibrentsavir combination. The safest and efficacy have not been determined in children of three or lesser years of age.
Geriatric Patients
The use of Glecaprevir in older patients can sometimes be not helpful as their aged condition can limit the beneficial effects of the drug.
Breastfeeding Mother
There are no studies on breastfeeding mothers related to Glecaprevir.
Pregnancy
The use of Glecaprevir is not recommended in pregnancy.
Drug Interactions
Certain medicines, like Rifampicin, Atazanavir, or Atorvastatin, should not be taken. The doctor should know about the medicine and can change the dose accordingly.
Drug Interactions:
Drug interaction changes the effects of the drug. It can sometimes increase the risk of severe side effects.
Some of the drug interactions are mentioned below,
Atorvastatin
The statins slow the removal of other drugs from the body, and Atorvastatin's metabolism decreases when combined with Glecaprevir.
Acetaminophen
The metabolism of Acetaminophen can decrease when combined with Glecaprevir.
Atazanavir
The excretion of the Glecaprevir can be decreased when combined with it.
Rifampicin
The excretion of the Glecaprevir can be decreased when combined with it.
Cyclosporine
The serum concentration of Cyclosporine can be increased when combined with Glecaprevir.
Carbamazepine
The metabolism of Carbamazepine can be decreased when combined with Glecaprevir.
Digitoxin
The serum concentration of Digitoxin can be increased when combined with Glecaprevir.
Digoxin
Glecapravir can decrease the excretion of Digoxin, which can result in increased serum levels of it.
Prazosin
Glecaprevir may decrease Prazosin's excretion rate, which may result in higher serum levels.
Contraindications of Glecaprevir Drug:
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The patient is allergic to Glecaprevir.
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Patient with a severe hepatic problem.
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Contraindicated in the patient having drugs Rifampicin or Atazanavir.
Cautious Use of Glecaprevir Drug:
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Patients with hepatic decompression or failure with Glecaprevir should discontinue the Glecaprevir drug.
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The overuse of alcohol or addiction to it can be problematic with the Glecaprevir drug.
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Patients with diabetes can cautiously use Glecaprevir.
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The patient must be diagnosed with hepatitis B or C virus infection.
Clinical Efficacy of Glecaprevir Along With Pibrentasvir:
The findings of clinical trials provide patient-related factors influencing Glecaprevir/Pibrentasvir efficacy.
1. Clinical Efficacy
The sustained virologic response rates at 12 weeks in all integrated patients. In this, all genotypes were given in 21 phase-3 clinical trials. SVR12 rates in patients administered Glecapravir /Pibrentasvir (n=4817 patients) ranged from 90.1 to 99.8 percent in the intention-to-treat population. In this integrated efficacy, 97.5 percent of the patients given Glecaprevir /Pibrentasvir have accomplished SVR12. SVR12 rates in patients administered Glecapravir/Pibrentasvir (n=1765 patients) range from 92.5 percent to 100 percent in the intention-to-treat population. 99.7 percent of intention-to-treat have achieved Glecaprevir/Pibrentasvir.
2. SVR12 rates in all HCV Genotypes
It is described in 13 phase-3 clinical trials. It has included 3585 patients who were given Glecaprevir/ Pibrentasvir. Of these, 1740(48.5 percent) patients were infected with HCV GT 1, 765 (21.3 percent) were HCV GT 2, 758 (21.1 percent) were HCV GT 3, and 322 (9.1 percent) were infected with HCV GT 4-6. This integration shows that SVR 12 rates were lower in a subpopulation of patients with HCV GT3.
3. SVR12 Rates
Patients with compensated cirrhosis or without cirrhosis were described in 14 phases -3; given the clinical trials, 34 00 patients were given Glecaprevir/Pibrentasvir. SVR12 rates in patients with cirrhosis were present in 8 phase-3 clinical trials, which included 923 patients with Glecaprevir/ Pibrentasvir. In this integrated efficacy, 97.3 percent were without cirrhosis and 98 percent with compensated cirrhosis.
4. SVR12 Rates By Treatment History
SVR12 rates in DAA-naive patients were presented in 9 phase-3 clinical trials that included 2535 patients who were given Glecaprevir/Pibrentasvir. SVR12 rates in DAA-experienced patients were shown in 4 phase-3 clinical trials that consisted of 219 patients administered. Glecaprevir/Pibrentasvir. In this efficacy, 97.7 percent of DAA-naive and 96.2 percent of DAA-experienced patients accomplished SVR12.
5. HIV/HCV Coinfection
SVR12 rates in patients with HCV and no HIV coinfection in 20 phase-3 clinical trials, including 4631 patients having Glecaprevir/Pibrentasvir. In the integrated report, 97.7 percent of patients have SVR12. SVR12 rates in patients with HCV HIV coinfection were in 2 phase-3 clinical trials, including 186 patients with Glecaprevir/Pibrentasvir. In integrated ports, 98.9 percent of the patients have accomplished SVR12.
6. Safety Analysis
Four thousand fifteen patients with 18 cohort studies for the safety population were selected for administration of Glecaprevir/Pibrentasvir. 2420(64.1 percent) patients reported adverse effects, and 125 (3.32 percent) patients reported severe adverse effects. Hence discontinuation of the drug Glecaprevir/Pibrentasvir was done on days 8 and 15. In clinical trials of ENDURANCE 4, a patient due to an ischemic attack discontinued it on 12 days, and in ENDURANCE 2, adverse effects were similar in the placebo and Glecaprevir/Pibrentasvir.
Results
The integrated efficacy analysis of 4817 patients showed that 97.5 percent with chronic HCV achieved SVR12. The safety analysis has 4015 patients, which showed 64.1 percent of patients with adverse effects and 0.1 percent with serious effects related to Glecaprevir/Pibrentasvir.
The integrated efficacy and safety analysis of Glecaprevir/Pibrentasvir confirmed that 8 or 12 weeks of drug Glecaprevir/Pibrentasvir treatment is effective for HCV GTs 1-6, including in patients with treatment experience or cirrhosis. Therefore, it is a better option for HIV/HCV.
